Dipartimento di Chimica Farmaceutica e Tossicologica, Universita di Napoli Federico II, Via D. Montesano 49, 80131 Napoli, Italy.
Recent Pat Anticancer Drug Discov. 2012 Sep;7(3):313-36. doi: 10.2174/157489212801820066.
The molecular chaperone heat shock protein 90 (HSP90) is essential for the folding stability, intracellular disposition and proteolytic turnover of many of the key regulators of cell growth, differentiation and survival. These essential functions are used by the cells during the oncogenesis process to allow the tumor transformation and facilitate the rapid somatic evolution. Inhibition of HSP90 would provide combinatorial blockade of a range of oncogenic pathways, antagonizing many of the hallmark traits of cancer. Several HSP90 inhibitors are currently under clinical trial investigation for the treatment of cancer. This review summarizes the current state and progress achieved in the development of HSP90 inhibitors targeting the N-terminal ATP pocket, C-terminal domain, different compartmentalized isoforms, and protein (cochaperones and/or client proteins)/HSP90 interactions. In the context of drug discovery, the most relevant patents which appeared recently in the literature are discussed as well.
分子伴侣热休克蛋白 90（HSP90）对于许多细胞生长、分化和存活的关键调节剂的折叠稳定性、细胞内分布和蛋白水解周转至关重要。在致癌过程中，细胞利用这些基本功能来允许肿瘤转化并促进快速的体细胞进化。HSP90 的抑制将为一系列致癌途径提供组合阻断，拮抗癌症的许多标志性特征。目前有几种 HSP90 抑制剂正在进行临床试验，以治疗癌症。这篇综述总结了针对 N 端 ATP 结合口袋、C 端结构域、不同分隔同工型以及蛋白质（共伴侣和/或客户蛋白）/HSP90 相互作用的 HSP90 抑制剂的开发现状和进展。在药物发现的背景下，还讨论了最近文献中出现的最相关的专利。
